It is critical that applicants follow the Research (R) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 1. Overview Information
Part 2. Full Text of the Announcement

Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

The National Center for Complementary and Integrative Health (NCCIH) is committed to the rigorous investigation of Mind and Body Interventions to determine their safety and usefulness. For the purposes of this FOA, Mind and Body Interventions are non-pharmacological approaches that include mind/brain focused interventions (e.g., meditation, hypnosis), body-based approaches (e.g., acupuncture, massage, spinal manipulation/mobilization), meditative movement approaches (e.g., yoga, tai-chi, qigong), or some combination of these approaches. More about the current Mind and Body Interventions supported by the NCCIH may be found at http://nccih.nih.gov/health/integrative-health.

Traditionally, exploratory clinical trials of Mind and Body Interventions recruit volunteers based on clinical indications with outcomes focused on symptom reduction or improvement in some specified functional outcome. Such research, whether positive or negative with respect to an intervention’s ability to modulate symptoms or functional outcomes, provides little information about how the intervention might work in relation to the putative underlying cause or mechanisms associated with the clinical condition. Nor does it offer insight into how the interventions may be optimized or improved. Thus, mechanistic studies of Mind and Body Interventions are critically needed prior to a full-scale efficacy study.

Generally, mechanistic studies of Mind and Body Interventions comprise three key elements. The first key element is the intervention itself, which commonly contains complex procedures or techniques administered by a trained practitioner, teacher, or is self-administered to improve function and/or to modulate or reduce symptoms with certain conditions such as pain and anxiety. The second key element is the biologically-based mechanism(s) or behavioral process(es) by which a given Mind and Body Intervention may exert its intended functional or clinical outcome. The mechanism(s) or process(es) may range widely from biochemical/molecular mechanisms to behavioral processes. Commonly studied mechanisms of action for Mind and Body Interventions include structural and/or functional changes in physiological systems, and networks including parasympathetic and sympathetic neural systems, cortical and subcortical neural networks, neuromuscular systems, or activation of endocrine, immunological, vascular and lymphatic systems. The third key element is the intended functional or clinical outcomes of the intervention.

The intent of this FOA, therefore, is to encourage research that studies Mind and Body Interventions in two phases. The first phase is to explore and identify underlying mechanisms of action for a Mind and Body Intervention and to develop methods to assess those mechanisms or processes. The second phase should focus on how the putative mechanism(s) or process(es) may be improved, refined, enhanced, or strengthened in relation to the functional outcome or clinical benefit of the intervention. NCCIH views the goal of the early-phase R61 of this grant award being provision of efficient and objective means for examining a proposed mechanism or process that could then be directly applied to improving and optimizing the benefit of a Mind and Body Intervention in the R33 phase.

The R61 Phase

The primary objective of the R61 phase supported under this FOA is to evaluate the effect of a proposed Mind and Body Intervention on a hypothesized biologically-based mechanism of action or behavioral process. Applicants should provide a clear and logical rationale for: (1) why the proposed mechanism(s) or process(es) are relevant to the Mind and Body Intervention to be studied, (2) how mechanism(s) or process(es) are related to a clinical condition or functional outcome associated with the intervention, and (3) how understanding such mechanism(s) or process(es) could optimize the intervention and lead to improved clinical or functional outcomes.

Applicants are expected to develop a detailed description of the Mind and Body Intervention they propose to use in this context. The proposed mechanism(s) or process(es) are expected to be assessed using objective, quantifiable, and reproducible measures. Applicants are also expected to develop detailed descriptions of the measures and a strong rationale for choosing such measures. In addition, applicants are expected to examine the evidence on whether the proposed mechanism(s) or process(es) can be manipulated directly or indirectly in human participants by other approaches beyond the original Mind and Body Intervention. Applicants are encouraged to refer to http://www.ClinicalTrials.gov for a review of the registered trials already underway or completed to help determine whether: 1) the results of ongoing trials can inform the design of the proposed study, and 2) the proposed study is innovative.

A randomized intervention design is encouraged for this phase of study. An intended clinical or functional outcome for the proposed intervention is not required for the R61 phase, but may be included to give a preliminary assessment of the relevance of the putative mechanism to the intended influence a functional or clinical outcome. While more than one mechanism or process may be proposed for and examined under the R61 phase, investigators are encouraged to choose one primary measure for the mechanism(s) of action or process(es). The effect of the intervention on the primary mechanism should be adequately powered statistically. An appropriate control group (or control groups) should be selected and justified to demonstrate the proposed primary mechanistic effect. Masking/blinding conditions should be clearly specified for study participants/patients, instructors/practitioners, outcome assessors, data analysts/statisticians, and principal investigators to intervention group assignments, primary mechanistic outcome measures, and clinical/functional outcome measures. Investigators are expected to review the NCCIH Study Accrual and Retention Plan (https://nccih.nih.gov/grants/policies/SARP).

If a device is used as part of the Mind and Body Intervention, investigators must contact the US Food and Drug Administration (FDA), prior to submitting an application, to determine whether an Investigational Device Exemption (IDE) application is necessary for the proposed clinical research. The R61/R33 application should explicitly state the status of an IDE, as appropriate.

Go/No-Go Criteria

In the R61 phase application, investigators are expected to describe a set of Go/No-Go Criteria (please see Section IV.2 Research Plan for detailed instructions) that will allow for a definitive assessment of whether the R61 phase provides sufficient evidence to support the subsequent proposed optimization strategy that would be examined under the R33 phase of the grant application. Key evidence in the Go/No-Go Criteria includes:

• Detect a clear effect size in the primary mechanistic outcome measure(s) by the proposed intervention.
• Provide adequate preliminary data to justify conducting the proposed optimization strategy under the R33 phase.
• Demonstrate that the delivery of the intervention(s) and the control intervention(s) under study can be delivered consistently as defined by a set of metrics.
• Demonstrate the safety and tolerability of the intervention(s) used in the study by a set of metrics.
• Demonstrate the ability to recruit and retain subjects in the clinical study with a pre-planned timeline for reaching the randomization target and estimated drop-out rate.
• By month 20 of the R61 award, submit R33 clinical study protocols and Data and Safety Monitoring Plan to NCCIH for review and approval.
• By month 21 of the R61 award, submit a R33 Transition Request Application .
• If appropriate, demonstrate that the changes in the primary mechanistic outcome measure(s) are associated with changes in the clinical or functional outcome(s) in the specified population.

While not required, investigators may also propose to evaluate how the frequency, duration, or other variations of the intervention may have differential impact on the primary mechanistic outcome(s).

Progress under the R61 phase will be administratively reviewed by NCCIH. Funding for and transition to the R33 phase is contingent on the following: 1) meeting the Go/No-Go Criteria articulated in the R61 phase, 2) the availability of funds, and 3) NCCIH and regulatory approval of the planned R33 activities (e.g., study documents, IRB, and if applicable IDE). If a device or a drug is proposed to enhance the Mind and Body Intervention in the R33 phase, then investigators must communicate with the FDA for determination about whether the R33 trial will need to be conducted under an Investigational New Drug application (IND) or Investigational Device Exemption (IDE) after NCCIH approval of the protocol and prior to R33 funding.

The R33 Phase

The primary objective of the R33 phase is to design and evaluate a strategy to optimize the effects of the Mind and Body Interventions on the hypothesized mechanisms or processes demonstrated in the R61 phase.

In general, there are three major types of intervention optimization strategies for studying the proposed mechanisms or processes. The first type may focus on modifying the complex Mind and Body Interventions per se, so that the active components of the intervention may be enhanced while the inactive or irrelevant components of the intervention may be minimized. To pursue this type of optimization strategy, it is common, in the R61 phase, to have demonstrated that the mechanistic effect of a complex Mind and Body Intervention would be at least moderately better than a well-controlled intervention lacking the presumed active component(s). The second type of optimization strategy may enhance the mechanistic effects of the proposed Mind and Body Interventions by adding other interventions (e.g., non-invasive devices, natural products, or pharmacological interventions) that have been previously shown to modulate the same mechanisms or processes to explore possible additive or synergistic effects. The third type of optimization strategy would be to select a targeted population that might benefit from the hypothesized mechanisms or processes modulated by the intervention. For this type of optimization strategy, it is important to be supported by preliminary evidence that the hypothesized mechanisms or processes are relevant for the proposed clinical population. Based on such preliminary results, the R33 phase would examine whether the mechanisms or processes using the proposed intervention significantly change and possibly amplify the mechanistic effect in the target populations. For the R33 phase, investigators may choose to optimize the proposed Mind and Body Intervention using any one or a combination of these optimization strategies.

The R33 phase of the study is expected to be fully powered to demonstrate the effect on the hypothesized mechanism(s) or process(es) by the optimized strategy in comparison to an appropriate control condition. Due to the pilot nature of the R33 phase, the proposed study is not expected to be fully powered to determine efficacy or effectiveness of the intervention. Nevertheless, examination of the correlation with clinical outcome(s) is of value for decisions about follow-on studies. In most cases, a randomized clinical design will be appropriate for the R33 phase, with the choice of the control group determined by the needs for testing the specific mechanism(s) or process(es). Masking of subjects and objective methods of assessment using masked raters should be employed whenever possible. Masking procedures should be clearly specified for the study participants/patients, instructors/practitioners, outcome assessors, data analysts/statisticians, and principal investigators.

The R33 phase is expected to provide a brief description of study participants, recruitment plans, milestones, and timeline. The proposed milestones for the R33 phase may be revised in accordance with activities carried out in the R61 phase. In addition, the R33 phase is expected to provide justifications, as appropriate, exploring the intervention's dose-response (i.e., frequency and duration of the intervention), initial safety, and tolerability data for the proposed manipulations and interventions. Although not required, secondary aims in the R33 may include: 1) further testing of the intervention’s feasibility, safety, and acceptability; 2) evaluation and optimization of the frequency or intensity of the intervention to determine impact on the proposed mechanism or process; and/or 3) development of functional biological signature or psychological process measures and clinical outcome measures feasible for use in larger efficacy and effectiveness trials.

This FOA provides support for up to two years (R61 phase) for Go/No-Go Criteria -driven testing of the intervention’s effect on a well-defined, hypothesized mechanism of action or process. By month 21 of the R61 award, the investigators will need to submit a R33 Transition Request Application . The R33 transition requests will undergo an administrative review by NCCIH to determine whether the Go/No-Go Criteria and other required conditions have been met, before a R33 award is made. In view of the exploratory nature of R61 studies funded via this FOA, it is anticipated that not all funded R61 projects will transition to the R33 phase. R33 awards are also dependent on the availability of funds.

If the R61 Go/No-Go Criteria are successfully achieved, there is a possibility of support of up to three additional years (R33 phase) for studies to design and evaluate optimization strategies to enhance the impact of the proposed Mind and Body Intervention on the hypothesized mechanism(s) or process(es). If an R33 is awarded, the results from the R33 phase studies should provide evidence to inform a decision about whether the proposed modifiable mechanism of the intervention is or is not correlated with the clinical outcome of interest. If the proposed mechanism is correlated with the outcome of interest, the results of the R33 could further inform whether the mechanistic insight and the strategy to manipulate the mechanism should be incorporated into further testing to optimize the efficacy or effectiveness of the intervention in a full scale clinical trial.

If the R61 phase study is not able to reach the Go criteria as defined at the initial award stage, due to a lack of statistically significant effect on the hypothesized mechanisms or processes, the investigators will be expected to submit a new R61 application to investigate a different mechanism of the intervention. If the R61 phase of the study can demonstrate a statistically significant effect on an alternative mechanism not included in the original application, or if the investigators are not able to provide adequate preliminary data to support the originally proposed R33 optimization strategy by the end of the R61 phase, the investigators will be expected to submit a new R33 application via the PAR-17-162 (R33) to propose a new optimization strategy for the Mind and Body Intervention based on the alternative mechanism and/or adequate preliminary data to support another optimization strategy. Such R33 applications will be peer reviewed before funding consideration. If the lack of the success of the R61 phase is simply due to the inability to reach the Go criteria on time, the investigators are expected to choose to terminate the R61 study and forgo transition to the R33 phase, or seek other funding to complete the Go criteria defined in the initial R61 award, and then submit a delayed R33 Transition Request Application to NCCIH for administrative review. There is no guarantee that the R33 transition request from the delayed application will be funded by NCCIH even if all the Go criteria are reached.

This FOA supports research exploring putative mechanisms or processes underlying Mind and Body Interventions intended for human participants. The mechanism(s) or process(es) proposed for the study can use epigenetic, biochemical, molecular, cellular, physiological, neurophysiological, or behavioral methods. They can be tissue- or organ- specific mechanisms or measures of psychosocial and behavioral processes, such as stress reactivity, self-regulation, sustained attention, or social, interpersonal, or somatic processes that are relevant to the proposed intervention. This FOA is not intended to support work exclusively focusing on the characteristics of practitioners or of healthcare settings in which the intervention is delivered. Such characteristics, however, may be included for study if a strong rationale can be made for their importance in modulating the putative underlying mechanism(s) or process(es) associated with an intervention.

Research applications submitted under this FOA are likely to cover a large and diverse group of complementary integrative health interventions, practices, and disciplines. NCCIH is, however, interested in: (1) interventions that have compelling evidence for potential health benefit; (2) interventions with evidence that they can exert a plausible and measurable biological or psychological effect; and (3) practices that are widely used by the American public. For this FOA, therefore, NCCIH considers the following topic areas/clinical outcomes to have high program priority for study with Mind and Body Intervention:

• pain and pain management;
• sleep and sleep disturbances;
• symptomatic conditions, such as those associated with menopause;
• management of mental health conditions commonly managed in primary care such as mild to moderate depression, or anxiety;
• behavior change to promote healthy behaviors such as healthy eating and physical exercise.

The following types of applications are not appropriate for this FOA:

• Exploratory studies that only utilize in vitro or animal models. (Basic mechanistic studies using in vitro or animal model systems are of high interest and priority to NCCIH; but at this time such applications should respond to the investigator-initiated R21 FOA PA-16-161).
• Clinical trials solely to estimate intervention effect size or power calculations for a future trial.
• Fully powered clinical trials proposing to test efficacy or effectiveness as the primary outcome. (Investigators aiming to test efficacy or effectiveness as the primary outcome should consult with NCCIH program staff and identify other appropriate FOAs.)
• Applications that do not propose to measure mechanisms or processes as described above.
• Applications that propose to test Mind and Body Interventions for the treatment or prevention of cancer or symptom management in a cancer or cancer survivor population. (Investigators interested in cancer treatment or prevention or cancer treatment of survivor patient populations should contact the National Cancer Institute). However, studies using a cancer or cancer survivor population to explore mechanisms or processes of Mind and Body Interventions for high priority topics as described above, which could be potentially generalizable to other non-cancer populations, may still be appropriate for this FOA.
• Applications that propose only the R61 phase or only the R33 phase will not be accepted under this FOA. (Applicants who already have sufficient preliminary data to progress to the R33 phase should apply directly to PAR-17-162 (R33) "Phase II Innovation Award for Mechanistic Studies of Mind and Body Interventions in NCCIH High Priority Research Topics)".

Applicants are encouraged to consult with NCCIH Scientific/Research staff before investigators begin developing their applications. (see Section VII, Agency Contacts). This early contact will provide an opportunity to clarify NCCIH policies and guidelines for clinical research and determine whether the research topic is a fit with NCCIH's mission and priorities. Investigators are encouraged to review the NCCIH Clinical Research Toolbox (http://NCCIH.nih.gov/grants/toolbox) to learn more about NCCIH's requirements for conducting clinical research.

See Section VIII. Other Information for award authorities and regulations.

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.

Higher Education Institutions

• Public/State Controlled Institutions of Higher Education
• Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

o Hispanic-serving Institutions

o Historically Black Colleges and Universities (HBCUs)

o Tribally Controlled Colleges and Universities (TCCUs)

o Alaska Native and Native Hawaiian Serving Institutions

o Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

• Small Businesses
• For-Profit Organizations (Other than Small Businesses)

Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)
• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• System for Award Management (SAM) (formerly CCR) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
• NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
• eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101).

Buttons to access the online ASSIST system or to download application forms are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

It is critical that applicants follow the Research (R) Instructions in the SF424 (R&R) Application Guide, including Supplemental Grant Application Instructions except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

• Descriptive title of proposed activity
• Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
• Names of other key personnel
• Participating institution(s)
• Number and title of this funding opportunity

The letter of intent should be sent to:

Martina Schmidt, PhD
National Center for Complementary and Integrative Health (NCCIH)
Telephone: 301-594-3456
Email: SchmidMa@mail.nih.gov

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed. As appropriate, Senior/Key Personnel should demonstrate their expertise and track record in clinical research, including expertise in the recruitment and retention of human subjects and methodological and statistical expertise. Also include recent collaborative clinical research efforts among members of the proposed team, if any. Describe the expertise within the research team in the measurement methods proposed (e.g., PET, fMRI, MRS).

All instructions in the SF424 (R&R) Application Guide must be followed. The R61 and R33 cannot be funded in the same fiscal year.

Budget Justification: For each budget year, indicate if the requested budget is for the R61 phase or the R33 phase. Describe the staffing for conducting the study as proposed and within specified timelines.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

Specific Aims:

In the single attachment allowed for the specific aims, applicants should provide brief background information to define the proposed Mind and Body Intervention, justify the importance of the topic area, outline the knowledge gap relevant to the proposed study, and provide rationale for the proposed hypotheses. This page should also include headers titled R61 Specific Aims and R33 Specific Aims with brief descriptions of key hypotheses as well as listing study population, number of participants, intervention groups, primary mechanistic measures, secondary/alternative mechanistic measures and associated clinical or functional outcomes, and alternative interpretations or strategies for each aim in the two phases of this project. In the R33 Specific Aims, the investigators should clearly indicate the optimization strategy and a brief justification with either preliminary data or existing literature for such a strategy. The investigators should also have at least one statement about innovation of the proposed hypothesis, and the general impact of the proposed study.

Research Strategy:

Clinical Significance, Rationale, and Biological or Psychological Relevance:

• Applicants should describe the general clinical significance of the proposed Mind and Body Intervention and a detailed definition of the proposed Mind and Body Intervention.
• Applicants should also describe and define the hypothesized primary mechanism. There must be a strong rationale, either based on relevant prior studies or the investigators own preliminary data, as to why the specific complementary and integrative intervention proposed is likely to impact this mechanism or process as well as potentially benefit the clinical condition under study, if relevant. The application should describe how the proposed project will advance knowledge of the mechanism of action of the intervention.
• Applicants should describe the relevance of the populations as well as associated clinical or functional outcomes to be studied in the R61 and R33 phases to the proposed intervention and the hypothesized mechanisms. Applicants may include a discussion of how the results of the proposed research (positive or negative) will guide decisions about further clinical or mechanistic studies.
• Approaches: This section should include an overall description as well as R61 and R33 specific descriptions. It should include the items listed below as appropriate:
• Intervention: 1) key preliminary data to justify the need to study the proposed Mind and Body Intervention either based on the existing literature or from unpublished data; 2) description of the Mind and Body Intervention to be tested, including any relevant and known biological processes, choice of dosing, intensity, duration, frequency, and grouping as appropriate.
• Primary Mechanisms: 1) Preliminary data and adequate justification based on relevant prior studies, either on biological mechanisms and clinical benefits in disease models, or from pilot human clinical studies conducted by the investigative team or from the scientific literature, should be presented as the rationale for the hypothesized primary mechanism(s). 2) Justification of the chosen measures to assess the hypothesized mechanism, including any preliminary data or existing literature to show how such a mechanism has been measured and studied, should be presented. 3) Detailed description of measures to assess the mechanism of action, including quantification method, and test of validity and reliability of the measures must be presented.
• Associated Functional/Clinical Outcomes: 1) preliminary data or existing literature to support the relevance of the functional or clinical outcomes to the proposed interventions and the hypothesized primary mechanisms; 2) clear justification and description of the target population; 3) specification of the measures for the functional or clinical outcomes quantitatively, either based on preliminary data or existing literature, and how these measures may relate to functional or clinical outcomes.
• R61 Methodology: 1) a schematic diagram for the R61 phase study design, including intervention and control groups, number of subjects per group, randomization scheme, duration of the interventions, primary mechanistic measure, and clinical/functional outcome measures; 2) describe and define the intervention and control groups, including inclusion/exclusion criteria; 3) justify the choices of the control groups and why such groups may adequately test the hypothesized mechanistic effects, including any preliminary data or evidence from the existing literature; 4) detailed description of the manipulation process, including relevant randomization, blinding, dosing, intensity, duration, frequency, and grouping information; 5) specify the effect change of the primary mechanistic measure and statistical analysis methods to be employed; 6) define the number of subjects per group and provide power calculation to demonstrate why the proposed numbers of subjects are sufficient to ascertain the effect of the proposed intervention on the hypothesized mechanism (preliminary data or existing literature may be presented to facilitate the justification and assumption of the power analysis); 7) any additional statistical issues related to interim analysis and missing data handling; 8) timeline and milestones for subject recruitment and retention; 9) discussion of alternative interpretations of results and strategies.
• R33 Methodology: 1) additional preliminary data or existing literature to support the proposed optimization strategy; 2) detailed description of the optimization strategy for the R33 phase with a schematic diagram; 3) describe and define the intervention and control groups, including inclusion/exclusion criteria; 4) justify the choices of the control groups and why such groups may adequately test the hypothesized mechanistic effects, including any preliminary data or evidence from the existing literature; 5) detailed description of the manipulation process, including relevant randomization, blinding, dosing, intensity, duration, frequency, and grouping information; 6) specify the hypothetical range of effect change of the primary mechanistic measure and the statistical analysis methods to be employed; 7) define the number of subjects per group and provide power calculation to demonstrate why the proposed numbers of subjects are sufficient to ascertain the effect of the proposed intervention on the hypothesized mechanism; 8) detailed analytic plan to assess the relationship between the mechanistic measures and the clinical or functional outcomes; 9) any additional statistical issues related to interim analysis and missing data handling; 10) timeline and milestones for subject recruitment and retention; 11) discussion of alternative interpretations of results and strategies.
• Secondary Assessments: description of all secondary assessments or measures including clinical, laboratory, physiological, behavioral, patient-centered, or other outcomes addressing the primary and secondary research questions. Use of patient reported outcomes, including those available through PROMIS, NIH Toolbox, and NeuroQoL, as well as non-traditional data collection approaches are encouraged if appropriate.

Go/No-Go Criteria for R61: Applications must provide this information in a section indicated by the heading "Go/No-Go Criteria for R61":

a. A clear effect size in changes in the primary mechanistic outcome measure(s) by the proposed intervention. Please describe the key content of the intervention and its controls, and specify the primary mechanistic outcome measure(s) and the secondary clinical outcome(s) quantitatively. For each proposed primary mechanistic outcome measure, provide references to describe and justify the measure.

i) A clear, definitive, and quantitative set of rules for the primary mechanistic outcome measure(s) to determine whether the intervention of interest can indeed modify the proposed mechanism and the metrics/thresholds of No-Go criteria regarding the primary mechanistic outcome measure(s) for the R33 phase.

ii) A clear and definitive decision rule should be provided to prioritize the mechanistic outcome measures if more than one is proposed, specify the direction of intervention-modified changes proposed, and how contradictory changes in the measures will be handled.

b. Adequate preliminary data (collected through prior studies, other concurrent studies, or the R61 phase study) to justify the proposed optimization strategy in the R33 phase. If the preliminary data for the optimization strategy is to be collected in other concurrent studies or the R61 phase of this application, a brief description of the planned experiments to generate such data and the anticipated outcomes that can justify the proposed R33 phase optimization strategy must be described.

c. A set of metrics that will demonstrate that the delivery of the intervention(s) and the control intervention(s) under study can be delivered consistently as defined by a set of metrics.

d. A set of metrics that will demonstrate the safety and tolerability of the intervention(s) used in the study by a set of metrics.

e. A set of metrics that will demonstrate the ability to recruit and retain subjects in the clinical study with a pre-planned timeline for reaching the randomization target and drop-out rate.

Data Management and Quality Control: data management and methods for monitoring quality; and methods for fidelity monitoring.

Subsequent Studies beyond the R61/R33: a brief summary of the subsequent studies, either with clinical efficacy as the primary goal or with further mechanistic investigation as the goal.

Data Safety Monitoring Plan

The investigators are encouraged to use the NCCIH template as a suggested format for the Data and Safety Monitoring Plan (DSMP). The DSMP should address the following elements:

• What data will be monitored?
• What policies and procedures will be implemented to ensure confidentiality of subject identifiers and accuracy/completeness of accumulating data throughout the monitoring process?
• In addition, NCCIH requires independent monitoring for research involving human subjects. Applicants should refer to the NCCIH Guidelines for Data and Safety Monitoring (http://nccih.nih.gov/grants/policies/data-safety-monitoring).

Letters of Support: Applicants are also encouraged to include documentation of the commitment of any collaborators, subcontractors, and consultants, as well as service agreements for personnel or facilities. Letters of commitment should be co-signed by the business official of the collaborating center.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

Appendix:

Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

When conducting clinical research, follow all instructions for completing PHS Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

All instructions in the SF424 (R&R) Application Guide must be followed.

See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov

Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

This initiative is not subject to intergovernmental review.

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review, NIH. Applications that are incomplete or non-compliant will not be reviewed.

In order to expedite review, applicants are requested to notify the NCCIH Referral Office by email at ScmidMa@mail.nih.gov when the application has been submitted. Please include the FOA number and title, PD/PI name, and title of the application.

Applicants requesting $500,000 or more in direct costs in any year (excluding consortium F&A) must contact a Scientific/ Research Contact at least 6 weeks before submitting the application and follow the Policy on the Acceptance for Review of Unsolicited Applications that Request $500,000 or More in Direct Costs as described in the SF424 (R&R) Application Guide. NCCIH Policy for applications requesting direct costs of $500,000 or more in any one year can be found at https://nccih.nih.gov/grants/policies/over500k.

Applicants are required to follow the instructions for post-submission materials, as described in the policy.

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

For this particular announcement, note the following:

The R61/R33 phased innovation grant supports highly innovative mechanistic studies of Mind and Body Intervention as well as a rapid translation of such mechanistic insights into clinically relevant optimization strategies. While highly innovative work often inherently carries a substantial scientific risk (i.e., the original hypothesis may not be proven), this risk can be substantially mitigated by properly designed Go/No-Go Criteria that would help determine whether at the end of the R61 phase the study is ready to move forward to the R33 phase. A well-planned R33 phase is only meaningful if the R61 phase is both innovative and well-designed. An R61/R33 grant application need not have preliminary data, extensive background material or preliminary information; however, they may be included if available. Appropriate justification for the proposed work can be provided through literature citations, data from other sources, or, when available, from investigator-generated data. Accordingly, reviewers will emphasize the level of innovation, the potential to significantly optimize the proposed intervention, and the rigor of the proposed experimental designs. Reviewers will assign a single impact score for the entire application, which includes the R61 phase, the Go/No-Go Criteria and the R33 phase.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Does the project address an important problem or a critical barrier to progress in the field? Is there a strong scientific premise for the project? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Is the hypothesized mechanism modifiable and optimizable to enhance the proposed Mind and Body Intervention? Is the proposed project likely to yield clear answers needed to proceed to the next step of research as proposed in this application?

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

Does the application provide strong evidence of necessary experience and expertise with the intervention, the study population, and the research methods to be employed? Does the investigative team have a track record of publishing the results of previous studies in high impact journals? Does the investigative team have adequate experience in recruiting clinical populations?

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

Does the proposed research have the potential to advance or transform the field by breaking ground for future clinical research? In the R61 phase, is the primary mechanism proposed novel for the intervention or the intended functional or clinical outcome? In the R33 phase, is the proposed optimization strategy novel for strengthening the primary mechanism?

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

R61 phase: 1) Is the proposed Mind and Body Intervention adequately described? 2) Are the methods and measures to study the hypothesized mechanism of action appropriate and/or well justified? 3) Are the choices of control group(s) appropriate to test the hypothesized mechanism? 4) Is the hypothesized mechanistic effect statistically powered with adequate justifications? 5) Is the need for the R61 phase well justified?

R33 Phase: 1) Does the R33 phase include sound methodology for (a) enhancing the initial impact on the mechanism of action from the R61 phase, and (b) evaluating associations between biological or psychological mechanisms and subsequent clinical or functional change? 2) Are enough preliminary data and/or evidence presented or to be collected for the proposed optimization strategy in the R33 phase to enhance the mechanistic effect? 3) Is the hypothesized mechanistic effect by the proposed optimization strategy statistically powered with adequate justifications? 4) Are the choices of control group(s) appropriate to test the proposed optimization strategy? 5) Are the outcome measures, dose/duration of study, appropriateness of inclusion/exclusion criteria, blinding, and sample size clearly justified and explained in the application? 6) Is the proposed design feasible and adequate to provide interpretable results?

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of children, justified in terms of the scientific goals and research strategy proposed?

Are the plans for recruitment outreach appropriate and are there follow-up procedures to ensure collection of data at stated intervals? Are the retention plans and practices described?

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

Does the application provide a reasonable assurance that the target sample size can be enrolled in the timeframe proposed? Does the application include information about the availability of the requisite subject pool in proposed clinical center(s)? If applicable, is there documentation of the commitment of any collaborators, subcontractors, and consultants, as well as service agreements for personnel and facilities?

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

R61 Go/No-Go Criteria and Timeline

Do the criteria define a definitive assessment of whether the intervention affects the hypothesized mechanism of action in a meaningful way that will justify the transition to the R33 phase? Is the additional preliminary data presented or to be collected strong enough to support the proposed optimization strategy for the R33 phase? Do the criteria describe feasible timelines and rates of subject recruitment and retention for the R61 phase of study? Are the R61/R33 Go/No-Go Criteria well defined to mitigate the high risk of the exploratory R61 phase of the study such that should the R61 phase fail, they will definitively prevent the proposal study to transition to the R33 phase?

For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of children to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

Not Applicable

For Revisions, the committee will consider the appropriateness of the proposed expansion of the scope of the project. If the Revision application relates to a specific line of investigation presented in the original application that was not recommended for approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident.

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

Not Applicable

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3) Genomic Data Sharing Plan (GDS).

For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by NCCIH, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

• May undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
• Will receive a written critique.

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications . Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and http://www.hhs.gov/ocr/civilrights/understanding/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.

Cooperative Agreement Terms and Conditions of Award

Not Applicable

When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

A final progress report, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 Award Term and Conditions for Recipient Integrity and Performance Matters.

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

eRA Service Desk (Questions regarding ASSIST, eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Telephone: 800-518-4726
Email: support@grants.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-710-0267

Wen G. Chen, PhD
National Center for Complementary and Integrative Health (NCCIH)
Telephone: 301-451-3989
Email: chenw@mail.nih.gov

Martina Schmidt, PhD
National Center for Complementary and Integrative Health (NCCIH)
Telephone: 301-594-3456
Email: schmidMa@mail.nih.gov

Shelley Carow
National Center for Complementary and Integrative Health (NCCIH)
Telephone: 301-594-3788
Email: carows@mail.nih.gov

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75.